Synthesis of tetrahydrochromenes and dihydronaphthofurans via a cascade process of [3 + 3] and [3 + 2] annulation reactions: mechanistic insight for 6-endo-trig and 5-exo-trig cyclisation.

Substituted tetrahydrochromenes and dihydronaphthofurans are easily accessible by the treatment of ß-tetralone with trans-ß-nitro styrene derived Morita-Baylis-Hillman (MBH) acetates through a formal [3 + 3]/[3 + 2] annulation. The reaction proceeds through a cascade Michael/oxa-Michael pathway with moderate to good yields. A DFT study was carried out to account for the formation of the corresponding six and five-membered heterocycles via 6-endo-trig and 5-exo-trig cyclization.

Synthesis of fully functionalised spiropyran pyrazolone skeletons via a formal [4 + 2] cascade process using ß-nitro-styrene-derived MBH-alcohols.

An efficient protocol was established to construct spiro pyrazolone tetrahydropyran scaffolds at ambient temperature under metal-free conditions. The reaction proceeded via formal [4 + 2] cyclisation of trans-ß-nitro-styrene-derived Morita-Baylis-Hillman (MBH) alcohol with α-arylidene pyrazolone. The reaction followed an oxa-Michael/Michael cascade pathway, resulting in the formation of new C-C and C-O bonds. Organocatalytic synthesis of spiropyrazolones using quinine-derived catalyst resulted in 94% enantiomeric excess (ee) and excellent (>20 : 1) diastereoselectivity.

Synthesis of trans N-Substituted Pyrrolidine Derivatives Bearing 1,2,4- triazole Ring.

BACKGROUND: 1,2,4-triazoles scaffolds display significant biological activities due to hydrogen bonding, solubility, dipole character, and rigidity. OBJECTIVE: The core motif of 1,2,4-triazoles plays a vital role in clinical drugs such as Rizatriptan (antimigraine), Ribavirin (antiviral), anastrozole (anticancer), etizolam (anxiolytic), estazolam (anticonvulsant), alprazolam (anti-hypnotic), letrozole (aromatase inhibitor), loreclezole (anticonvulsant), trazadone (antidepressant) etc. Methods: Epoxide ring opening of tert-butyl 6-oxa-3-azabicyclo [3.1.0] hexane-3-carboxylate followed by methylation under basic conditions and de-protection gave the corresponding trans 1-(4- methoxypyrrolidin-3-yl)-1H-1,2,4-triazole hydrochloride salt as the precursor. This precursor on reaction with substituted benzoyl chlorides and benzyl bromides gave the desired amide and amine products. RESULTS: A library of 14 N-substituted pyrrolidine derivatives i.e. trans3-methoxy-4-(1H-1,2,4-triazol- 1-yl) pyrrolidin-1-yl) (phenyl)methanone and trans 1-benzyl-4-methoxypyrrolidin-3-yl)-1H-1,2,4- triazole were prepared. CONCLUSION: Eight novel amides (6a-h) and six amines (8a-f) derivatives were synthesized using 1-(4- methoxypyrrolidin-3-yl)-1H-1,2,4-triazole 4 salt with substituted benzoyl chlorides and benzyl bromides.